Language disorders in children with congenital hypothyroidism

Introduction Congenital hypothyroidism (CH) represents one of the most common preventable causes of mental retardation. If fetal hypothyroidism develops, untoward effects may be shown in certain organ systems, including the central nervous system. CH may be associated with hearing and language impairment. It is possible that this impairment may worsen with delay of therapy. Problems in language, auditory processing, and reading may persist in hypothyroid children, particularly if their treatment with l-thyroxin is delayed into the third week of life. The aim of this study is to estimate the extent of language disorder and detect the factors influencing language acquisition in children with CH. Patients and methods This study included 60 children. The study group included 40 children who complained of CH. The age range of this group was 3–8 years. The children of the study group were divided according to the level of thyroid stimulating hormone (TSH) and T4 into two subgroups. The G1 subgroup included children with controlled CH and subgroup G2 included children with uncontrolled hypothyroidism. The results of the study group were compared with those of another group (control group), which included 20 children; both groups were matched for age and sex. The children of both groups were subjected to the protocol of language assessment. Results and conclusion The current study showed that the children with uncontrolled CH show delayed language, mental, social age, and intelligence quotient in comparison with children with controlled hypothyroidism and normal children. There is a need for the diagnosis and treatment of children with CH as soon as possible after birth, preferably no later than the second week of life. It is also important to screen hypothyroid children for hearing problems and to provide remediation in language and reading.


Introduction
Hypothyroidism results from the deficient production of thyroid hormone or defect of thyroid hormone receptor activity. Most cases of congenital hypothyroidism (CH) are not hereditary and result from thyroid dysgenesis. Some cases may be familial, usually caused by one of the inborn errors of thyroid hormone synthesis [1].
Children born with CH who lack thyroid hormone during early period of development are at risk of brain damage and mental retardation [2].
The prevalence of CH reported on the basis of nationwide programs for neonatal screening is 1/4000 infants worldwide. The prevalence is lower in Black Americans (1/32 000) and higher in Hispanics and Native Americans (1/2000). The female to male ratio is 2:1 [1]. Also, Fuggle et al. [3] reported that CH may be associated with hearing and language impairment. It is possible that this impairment may worsen with delay of therapy. The problems in receptive language, auditory processing, and reading may persist in hypothyroid children, particularly if their treatment with l-thyroxin is delayed into the third week of life [3].
On psychometric tests, the hypothyroid group was observed to perform significantly lower than nonimpaired hypothyroid at 3 years of age, but seemed to catch up by age 5 and did not differ on an expressive language test administered at the age of 7 years [4], whereas Rovet and Ehrlich [5] reported that early identification and treatment of CH with newborn screening is associated with almost complete elimination of mental retardation and significantly improved intellectual functioning; however, intelligence quotients (IQs) are significantly and persistently reduced, and subtle impairments may occur in language memory and attention.
The aim of this study is to estimate the extent of language disorder and detect the factors influencing language acquisition in children with CH. The control group G3 included 20 children. There were 11 (55%) males and nine (45%) females (mean age: 70.8±14.5 months, range: 43-90 months). The children of this group had normal levels of TSH and T4.

Patients and methods
The patient and control groups were subjected to the following: (1) Full assessment of personal and medical history from parents that included natal and perinatal history.
(2) Ear, nose, and throat examination of the children.
(4) Audiological evaluation: Audiological evaluation was carried out to ensure normal hearing sensitivity (tympanogram, pure tone audiometry, auditory brain stem evoked response to identify hearing sensitivity The Arabic Language Test was used [9]. The language test items include attention of the child by observation, receptive part of the semantics, expressive part of the semantics, receptive part of the syntax, the expressive part of syntax, pragmatics, and prosody [9].

Statistical analysis
Data were collected and analyzed using SPSS software (version 19 for Windows; SPSS Inc., Chicago, Illinois, USA). An independent-sample T-test was used to compare quantitative data and the χ 2 -test was used to compare qualitative data.

Results
The current study was carried out on 60 children; the study group included 40 children. There were 13 (32.5%) males and 27 (67.5%) females.
The children of the study group were divided according to the level of TSH and T4 into two groups. G1 subgroup included children with controlled CH and subgroup G2 included children with uncontrolled hypothyroidism. The control group G3 included 20 health children with normal TSH and T4. Table 1 shows the sociodemographic data of the groups.
Intelligence quotient, mental, social age, and language assessments Our study showed that the mean IQ of the children in G1 was 78.7±10.9 (range: 51-92), the mean IQ of the children in G2 was 56.3±5.6 (range: 50-66), and the mean IQ of the children in G3 was 81.5±17.5 (range: 48-99).
The mean mental age of the children in G1 was 61.9±17.1 (range: 25-85), the mean mental age of the children in G2 was 42.6±18.6 (range: 22-80), and the mean mental age of the children in G3 was 74.3±18.7 (range: 25-93).
The mean language age of the children in G1 was 42.4± 18.3 (range: 25-90), the mean language age of the children in G2 was 22.8±12.6 (range: 2-40), and the mean language age of the children in G3 was 56±20.3 (range: 24-84).
The previous data indicate statistically significant differences between the study and the control group in the IQ and language age (P<0.05), highly statistically significant differences between the study and the control group in the mental and social age (P<0.01), and highly statistically significant differences between G1 and G2 in the IQ, mental, social, and language age (P<0.01). Table 2 shows a comparison between the three groups in IQ test, mental, social, and language age. Figure 1 shows a comparison between the study and the control groups in the IQ test, mental, social, and language age.
A highly positive significant correlation was found between the language, mental, social age, and IQ with the level of T4 in G1 and G2 (r=0.76).
A highly negative significant correlation was found between the language, mental, social age, and IQ  IQ, intelligence quotient. *,** Level of significance when P<0.05.

Figure 1
Comparison between study and control as regarding IQ test, mental, social and language age.
with the level of TSH in G1 and G2 (r=−0.87). Table 4 shows the correlation between language, mental, social, IQ, and the level of TSH and T4.

The audiological assessment
There was no statistical difference between the study and control groups in the audiological evaluation (P>0.05). Table 5 shows a comparison between study and control groups in tympanometry and audiometry.

Discussion
CH represents one of the most common preventable causes of mental retardation. If fetal hypothyroidism develops, unwanted effects may be found in certain organ systems, including the central nervous system and skeleton. However, most infants with CH appear normal at birth [10]. Thyroxin is a major regulator of the mammalian brain development; an important role for thyroxin can be expected from early fetal life until the completion of central nervous system growth, several years beyond birth. Lack of thyroxin, during the critical period of central nervous system responsiveness to this hormone, results in delay of myelination and dendritic arbor [11].
The current study aimed to investigate the language developmental outcomes of the children with CH (study group) in comparison with children with normal thyroid functions (control group); there was a statistically significant difference between the children with hypothyroid function and children with normal thyroid function in IQ, mental, and social age. Moreover, there was a highly statistically significant difference between the children with controlled hypothyroidism and those with noncontrolled hypothyroidism in the IQ, social, and mental age. Miller et al. [12] reported that the treated hypothyroid group had significantly increased verbal memory retrieval. Results suggest that specific memory retrieval deficits associated with hypothyroidism can resolve after replacement therapy with l-thyroxine.
Koibuchi and Chin [13] studied children with severe CH, treated at a mean age of 5 weeks with l g/kg/day of l-thyroxine; they had mean IQ scores 10-22 points below that of their siblings from 18 months until 12 years of age (the last time point studied), whereas those with moderate CH had IQ scores similar to those of control children.
Hrytsiuk et al. [14] carried out neurological and psychological assessments on 30 patients aged 2.7-21 years (mean: 9.4 years) who were being treated for hypothyroidism starting before the age of 2 years. Their IQ scores were within the normal range (71-122; mean: 92.4), but 77% showed at least one sign of impaired brain function. Clumsiness was found in 33%, behavior disorders in 23%, language disorders in 20%, learning disorders in 26%, squint in 53%, nystagmus in 10%, and minor motor disorders in  50% [14]. The current study is in agreement with that of Miller et al. [12], Koibuchi and Chin [13], and Hrytsiuk et al. [14], who showed affection of IQ, language development, and mental age in CH.
MRI showed that signal intensities from various white matter areas were comparable in untreated patients and control participants. There was also no change in signal intensities after thyroxine replacement. MRI was shown to have identify a delay in myelination in patients with untreated CH; an improvement was documented after thyroxine replacement [15].
The current results obtained from the Arabic language test indicated a significant difference between children with hypothyroidism and children with normal thyroid function in the language age. Moreover, there was a highly statistically significant difference between the children with controlled hypothyroidism and those with noncontrolled hypothyroidism in language age. These results are in agreement with those of Glorieux et al. [16], who studied the mental development of hypothyroid infants at the age of 12, 18, and 36 months and found that there was no difference between the global quotient in the 12 months. However, at 18 months and 36 months of age, the hypothyroid group had a significantly lower mean global quotient than the control group. They stated that their results may represent the manifestations of brain damage that occur even with early detection and treatment of hypothyroidism [16].
Fuggle et al.
[3], Rovet et al. [1] and Rovet and Ehrlich [5] found significantly improved intellectual functioning; however, significantly and persistently reduced intellectual quotients with subtle impairments may occur in language memory and attention in hypothyroid children. Miller et al. [12] reported in their study that the treated hypothyroid group had significantly increased verbal memory retrieval. Results suggest that specific memory retrieval deficits associated with hypothyroidism can resolve after replacement therapy with l-thyroxine [12]. Our results are not in agreement with those of Denman [17], who found that the CH group did not differ from control children on tests of phonological processing (WJRMT Word Attack), writing (test of written language; TOWL), or spelling (WRATR spelling). The results of the supplementary tests also indicated no differences in language and memory tasks [17].
Komur et al. [18] reported that cognitive, language, and global motor scores in addition to receptive communication, expressive communication, fine motor, and gross motor subscores in children with CH were statistically significantly lower than those in the control group, and their study concluded that despite early and effective treatment in newborns with CH, retardation in neurological developmental was detected. This could be related to influences on neurodevelopment in the intrauterine period. Current data are in agreement with our results as uncontrolled hypothyroidism score lower than controlled hypothyroid children as well as normal ones regarding language development [18]. Also, our results in agreement with those of Gejão and Lamônica [19], who reported that most of the children in their study showed adequate performance in the skills evaluated, whereas for children with altered performance, larger deficits were observed in the language section, in the expressive aspects, and in the cognitive section.
Bargagna et al. [20] reported in their study that the mean total scores of the study group in cognitive tests were within the normal range; instead, motor and language impairments were noted. These skills are significantly correlated with pretreatment serum thyroxine. This study supports our results as language impairment is very crucial in hypothyroid children, and screening and early detection of hypothyroid babies is essential [20].
The current study concludes that there is a need for the diagnosis and treatment of children with CH as soon as possible after birth, preferably no later than the second week of life. It is also important to screen hypothyroid children for hearing problems and to provide remediation in language and reading.

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Conflicts of interest
There are no conflicts of interest.